Sepsis is a systemic inflammatory response that is the second-leading cause of death in non-coronaty ICU patients suffering trauma from accidents or major surgery. One approach to address this problem is through a better understanding of inflammatory response to pathogens and tissue injuries. It has long been known that foreign pathogens and their molecular elements, such as lipopolysaccharide (LPS), could induce the production of many mediators involved in septic shock. Recent studies indicate that high mobility group box 1 protein (HMGB1), which will be secreted by necrotic cells in tissue injuries, mediates downstream inflammatory response in sepsis in both animal models and human patients. Our lab has recently developed a yeast-derived HMGB1, which did not induce inflammatory response by itself. Therefore, we hypothesize that yeast-derived HMGB1 will amplify the inflammatory effect of LPS and the mechanisms leading to excessive activation of inflammatory mediator cascades.